Weight Loss in Cancer Patients Correlates with p38β MAPK Activation in Skeletal Muscle

Abstract

Unintentional weight loss due to muscle wasting is a major threat to cancer survival without a defined etiology. We previously identified in mice that p38β MAPK mediates cancer-induced muscle wasting by stimulating catabolism. However, whether this mechanism is relevant to humans is unknown. In this study, we recruited men with cancer and weight loss (CWL) or weight stable (CWS), and non-cancer controls (NCC), who were consented to rectus abdominis (RA) biopsy and blood sampling (n = 20/group). In the RA of both CWS and CWL, levels of activated p38β MAPK and its effectors in the catabolic pathways were higher than in NCC, with progressively higher active p38β MAPK detected in CWL. Activated p38β MAPK correlated with weight loss. Plasma analysis for factors that activate p38β MAPK revealed higher levels in inflammatory cytokines, as well as Hsp70 and Hsp90 in CWS and/or CWL. Thus, p38β MAPK activation appears a key event associated with weight loss in cancer patients.